由 MTCH2 和 F-ATP 合成酶介导的线粒体通透性转换有助于铁中毒防御。

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Lishu Guo
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引用次数: 0

摘要

线粒体通透性转换孔(PTP)是位于线粒体内膜上的一个钙离子依赖性孔道,它的打开会引发线粒体外膜通透性(MOMP)并诱导细胞器破裂。然而,PTP 诱导 MOMP 的基本机制仍不清楚。线粒体载体同源物 2(MTCH2)通过促进线粒体招募 tBID 来介导 MOMP 过程。在这里,我们发现 MTCH2 与环嗜蛋白 D(CyPD)结合,并通过与亚基 j 的相互作用促进 F-ATP 合酶的二聚化。MTCH2 与亚基 j 之间的相互作用协调了 MOMP 和 PTP,从而介导了线粒体通透性转换的发生。敲除 CyPD、MTCH2 和 j 亚基可使细胞对 RSL3 诱导的铁中毒明显敏感,而 MitoTEMPO 可阻止这种敏感性,这表明线粒体通透性转换介导了铁中毒防御。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial permeability transition mediated by MTCH2 and F-ATP synthase contributes to ferroptosis defense.

The opening of the mitochondrial permeability transition pore (PTP), a Ca2+-dependent pore located in the inner mitochondrial membrane, triggers mitochondrial outer membrane permeabilization (MOMP) and induces organelle rupture. However, the underlying mechanism of PTP-induced MOMP remains unclear. Mitochondrial carrier homolog 2 (MTCH2) mediates MOMP process by facilitating the recruitment of tBID to mitochondria. Here, we show that MTCH2 binds to cyclophilin D (CyPD) and promotes the dimerization of F-ATP synthase via interaction with subunit j. The interplay between MTCH2 and subunit j coordinates MOMP and PTP to mediate the occurrence of mitochondrial permeability transition. Knockdown of CyPD, MTCH2 and subunit j markedly sensitizes cells to RSL3-induced ferroptosis, which is prevented by MitoTEMPO, suggesting that mitochondrial permeability transition mediates ferroptosis defense.

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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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